Pencil Beam Scanning Bragg Peak FLASH Technique for Ultra-High Dose Rate Intensity-Modulated Proton Therapy in Early-Stage Breast Cancer Treatment

SIMPLE SUMMARY: Breast cancer is the most prevalent form of cancer worldwide and is projected to affect one in every eight American women over their lifetimes; radiation therapy (RT) is utilized for most breast cancer patients’ treatments. Our study aimed to evaluate a novel Bragg peak, ultra-high dose rate (FLASH), proton radiotherapy (PRT) technique that can potentially decrease radiotherapy toxicities. Clinically viable Bragg peak FLASH treatment plans were generated for breast cancer patients who were treated with conventional PRT. Across dosimetric standards of care for healthy and cancerous tissues, we observed feasible breast cancer treatment delivery and high plan quality while maintaining an ultra-high dose rate. Therefore, delivering proton FLASH-RT for breast cancer may reduce toxicities and improve the therapeutic ratio. ABSTRACT: Bragg peak FLASH-RT can deliver highly conformal treatment and potentially offer improved normal tissue protection for radiotherapy patients. This study focused on developing ultra-high dose rate (≥40 Gy × RBE/s) intensity-modulated proton therapy (IMPT) for hypofractionated treatment of early-stage breast cancer. A novel tracking technique was developed to enable pencil beaming scanning (PBS) of single-energy protons to adapt the Bragg peak (BP) to the target distally. Standard-of-care PBS treatment plans of consecutively treated early-stage breast cancer patients using multiple energy layers were reoptimized using this technique, and dose metrics were compared between single-energy layer BP FLASH and conventional IMPT plans. FLASH dose rate coverage by volume (V(40Gy/s)) was also evaluated for the FLASH sparing effect. Distal tracking can precisely stop BP at the target distal edge. All plans (n = 10) achieved conformal IMPT-like dose distributions under clinical machine parameters. No statistically significant differences were observed in any dose metrics for heart, ipsilateral lung, most ipsilateral breast, and CTV metrics (p > 0.05 for all). Conventional plans yielded slightly superior target and skin dose uniformities with 4.5% and 12.9% lower dose maxes, respectively. FLASH-RT plans reached 46.7% and 61.9% average-dose rate FLASH coverage for tissues receiving more than 1 and 5 Gy plan dose total under the 250 minimum MU condition. Bragg peak FLASH-RT techniques achieved comparable plan quality to conventional IMPT while reaching adequate dose rate ratios, demonstrating the feasibility of early-stage breast cancer clinical applications.